From Lewis Blevins, MD – LH and FSH are produced by the pituitary gland under the regulation of pulsatile secretion of GnRH from the hypothalamus. LH stimulates the Leydig cells of the testes to produce testosterone. Testosterone is “measured” by and thus regulated by the hypothalamus and pituitary gland in a classic negative feedback way. FSH stimulates the Sertoli cells to do a number of important things including the development of sperm and the production of a number of different proteins including androgen-binding protein, activin, and inhibin. Inhibin acts on the pituitary to inhibit FSH secretion.
Testosterone circulates as a free molecule but most of it is bound to proteins, sex-hormone binding globulin (SHBG) and albumin. Obesity and some liver diseases can lower SHBG and thus total testosterone but free testosterone levels may be normal. In general, I check total and free testosterone levels. The total is a good surrogate for evaluation and management provided there is a correlation between total and free levels. I find free levels to be more useful than total levels in elderly and obese men and those with liver dysfunction.
In the genital tissues and prostate gland testosterone is converted to dihydrotestosterone by the enzyme 5-alpha reductase.
Hyperprolactinemia disrupts the cyclical and periodic secretion of GnRH from the hypothalamus and can shut down LH and FSH production causing low testosterone levels and infertility. LH and FSH levels may be inappropriately normal in the setting of a low or low-normal testosterone.
Men with testicular failure will have low testosterone levels along with elevations in LH and FSH. The LH is elevated because the Leydig cells in the testicles are unable to make testosterone. The FSH is elevated when the Sertoli cells fail to make inhibin. These men are said to have “primary hypogonadism.” Causes include Klinefelter’s syndrome, testicular trauma, infections (mumps), surgery, chemotherapy, etc.
Some men with gonadotropin-producing pituitary adenomas will have elevations in LH and/or FSH with low testosterone levels because the gonadotropins do not work and the tumor compromises normal LH and FSH production by the remaining normal pituitary gland. Rarely, a man will have elevations in testosterone when the gonadotropins do work in the setting of a gonadotropin-producing pituitary adenoma.
Most patients with hypothalamic or pituitary dysfunction will have low or low-normal LH and FSH levels in the setting of low or low-normal testosterone levels. These men are said to have “central hypogonadism.” Causes include a myriad of pituitary and hypothalamic disorders, Kallman’s syndrome, septo-optic dysplasia, etc.
Semen analysis is a means of assessing the adequacy of the hypothalamic-pituitary-testicu
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